Selective accretion of cytoprotectant in radiation-sensitive tissues and uses thereof

Abstract

The disclosure relates to the treatment of primary and metastatic cancer using radiation. Specifically, the disclosure relates to methods providing for the selective accretion of cytoprotective agent in tissues and/or organs, sensitive to radiation that are adjacent to malignant tumors prior to radiation of the tumors at a dose that otherwise would be toxic to the tissues and/or organs, but are necessary to achieve ablative outcome on the tumors.

What is claimed: 
     
       1. A method for treating a pancreatic cancer patient with a combination therapy, comprising:
 a. administering to the patient a therapeutically effective, orally dosed cytoprotective pro-drug that is S-2-(3-amino propylamino)ethyl dihydrogen phosphorothioate at between 15 minutes and 30 minutes prior to exposure to a stereotactic fractionated radiation, the patient having at least one of: a primary, and a metastatic cancer in the pancreas adjacent to at least one of: a duodenum, and a jejunum, wherein a metabolite of the therapeutically effective, orally dosed S-2-(3-amino propylamino)ethyl dihydrogen phosphorothioate is configured to selectively accrete in at least one of: the duodenum, and the jejunum; and 
 b. timely exposing the pancreas to the stereotactic fractionated radiation. 
 
     
     
       2. The method of  claim 1 , wherein the step of exposing comprises administrating to the patient a total radiation dose of between about 50 Gray (Gy) and about 208 Gy. 
     
     
       3. The method of  claim 1 , wherein radiation is administered in between 1 and about 5 fractions. 
     
     
       4. The method of  claim 3 , wherein the radiation is administered in between 3 and 5 fractions of 10 Gy and 17 Gy per fraction, so long as the total dose is above 50 Gy. 
     
     
       5. The method of  claim 1 , wherein the therapeutically effective orally dosed cytoprotective pro-drug that is S-2-(3-amino propylamino)ethyl dihydrogen phosphorothioate comprises between about 250 mg/kg and about 1000 mg/kg. 
     
     
       6. The method of  claim 1 , wherein the predetermined time prior to exposure to radiation is about 25 minutes. 
     
     
       7. A method of protecting at least one of: a duodenum, and a jejunum in a patient in need of a high dose radiation, from an exposure to the high dose radiation to a pancreas, comprising a step of administering to the patient an oral composition comprising a pharmaceutically effective concentration of an orally dosed pro-drug that is S-2-(3-amino propylamino)ethyl dihydrogen phosphorothioate having a metabolite adapted to selectively accrete in at least one of: the duodenum, and the jejunum, wherein the oral composition is administered at between about 15 min. and about 30 min. prior to a administration of a stereotactic fractionated radiation. 
     
     
       8. The method of  claim 7 , wherein the high-dose radiation has a total dose of a least 50 Gy. 
     
     
       9. The method of  claim 7  wherein the stereotactic fractionated radiation further comprises using fractionated stereotactic body radiation therapy, exposing the pancreas to between 1 and about 5 irradiation fractions. 
     
     
       10. The method of  claim 9 , wherein the high dose radiation has a total radiation dose of between about 50 Gy and about 208 Gy. 
     
     
       11. The method of  claim 9 , wherein the radiation is administered in between 3 and 5 fractions of 10 Gy and 17 Gy per fraction, so long as the total dose is at least 50 Gy. 
     
     
       12. The method of  claim 11 , wherein the therapeutically effective oral dose of the orally dosed pro-drug that is S-2-(3-amino propylamino)ethyl dihydrogen phosphorothioate is between about 20 mg/kg and about 81 mg/kg.